Ionizing Radiation Promotes Epithelial-Mesenchymal Transition Phenotype and Stem Cell Marker in The Lung adenocarcinoma: In Vitro and Bioinformatic Studiesc.

OBJECTIVE

Ionizing radiation (IR) is one of the major therapeutic approaches in the non-small cell lung cancer (NSCLC); however, it can paradoxically result in cancer progression likely through promoting epithelial-mesenchymal transition (EMT) and the cancer stem cell phenotype. Therefore, we aimed to determine whether IR promote EMT/CSC and to investigate the clinical relevance of EMT/CSC hallmark genes.

MATERIALS AND METHODS

In this experimental and bioinformatic study, A549 cell line was irradiated with a high dosage (6 Gy) or a fractionated regimen (2 Gy/day for 15 fractions). The EMT-related features, including cellular morphology, migratory and invasive capacities were evaluated using scratch assay and transwell migration/invasion assays. The mRNA levels of EMT-related genes (), stemness-related markers () and the ratio were evaluated via real-time polymerase chain reaction (PCR). The clinical significance of these genes was assessed in the lung adenocarcinoma (LUAD) samples using online databases.

RESULTS

Irradiation resulted in a dramatic elongation of cell shape and enhanced invasion and migration capabilities. These EMT-like alterations were accompanied with enhanced levels of and as well as an enhanced ratio. TCGA analysis revealed that, and were downregulated. Additionally, correlations between and was positive. Kaplan-Meier survival analysis identified lower expression of and and increased expression of , and as well as ratio predict overall survival. Additionally, downregulation of and upregulation of and could predict a shorter first progression.

CONCLUSION

Altogether, these findings demonstrated that IR promotes EMT phenotype and stem cell markers in A549 cell line and these genes could function as diagnostic or prognostic indicators in LUAD samples.